The increase in the number of patients going on dialysis in recent years is creating problems in terms of both patient QOL and national medical care expenditures. In the case of many chronic kidney diseases, including chronic glomerular nephritis, diabetic nephropathy and polycystic kidney disease, the course of the disease is progressive, and unless treatment is effective, these diseases ultimately result in loss of kidney function, eventually leading to dialysis due to renal failure. At present, dialysis treatment costs for treating kidney diseases (renal failure) exceeds one trillion yen, accounting for roughly 3% of all medical care expenditures, and the number of patients suffering from kidney damage is increasing annually. There are currently roughly 300,000 to 400,000 artificial dialysis patients in Japan, and medical costs required to undergo dialysis treatment for one month are said to be about 400,000 yen in the case of outpatient hemodialysis and 350,000 to 700,000 yen in the case of continuous ambulatory peritoneal dialysis (CAPD).
Among kidney diseases, glomerular epithelial cell disorders refer to disorders in which the glomerular epithelium is subjected to functional or structural damage due to various causes. Here, glomerular epithelial cells are referred to as podocytes, and are highly differentiated cells that line the outer surface of the glomerular basement membrane (GEM). Podocytes are a determinate component of the filtration barrier, and mutations in the genes of nephrin, podocin, α-actinin-4 and the like have been found to cause kidney disease-associated proteinuria (Schmid, H., et al., J. Am. Soc. Nephrol., Vol. 14, p. 2958-2966 (2003); Mundel, P. & Shankland, S. J., J. Am. Soc. Nephrol., Vol. 13, p. 3005-3015 (2002)). In addition, podocytes regulate glomerular filtration rate in response to changes in perfusion pressure by reacting to changes in pressure in glomerular capillaries (Mundel, P., et al., 2002, supra; Morton, M. J., J. Am. Soc. Nephrol., Vol. 15, p. 2981-2987 (2004); Pavenstadt, H., et al., Physiol. Rev., Vol. 83, p. 253-307 (2003)). In this manner, since glomerular epithelium containing podocytes fulfills an important role in the waste filtration function of the kidneys, it is imperative to prevent disorders of the glomerular epithelium from progressing to renal sclerosis so as not to allow further increases in the number of dialysis patients.
On the other hand, kidney diseases are not limited to disorders of the glomerulus, but also include diseases affecting renal tubules. Renal tubules are formed from the proximal renal tubule, the loop of Henle, the distal renal tubule and the renal collecting duct. If an abnormality occurs in the function of the renal tubules for some reason, various diseases may occur throughout the body. Examples of diseases of the proximal renal tubule include Fanconi's syndrome, aminoaciduria and renal glycosuria, while distal renal tubular acidosis is known to be a typical example of a disease of the distal renal tubule.
As chronic kidney disease progresses, since the functions possessed by a normal kidney are lost, effects extend to various organs throughout the body, typically resulting in uremia. Specific examples of disorders that occur include central nervous system disorders, peripheral nervous system disorders, cardiovascular disorders, gastrointestinal disorders, vision/ophthalmic disorders, blood/coagulation disorders, immune disorders, endocrine disorders, skin disorders, bone/joint disorders, electrolyte disorders and acid-base balance disorders. In these cases, artificial dialysis for preventing uremia is essential for the treatment of chronic kidney diseases, and kidney transplant is the only radical treatment that ensures a complete recovery. However, it is impossible for all patients with chronic kidney diseases to undergo kidney transplant due to a shortage of donors. Ever since dialysis treatment was first performed on patients with kidney diseases in the 1920s, there has yet to be developed a treatment method that places a reduced burden on the patient.
It has been determined from research by M. Dezawa, one of the inventors of the present invention, that multilineage-differentiating stress enduring cells (Muse cells) expressing surface antigen in the form of stage-specific embryonic antigen-3 (SSEA-3), which are present in mesenchymal cell fractions and can be obtained without going through an induction procedure, are responsible for the pluripotency possessed by mesenchymal cell fractions, and that they have the potential for application to disease treatment aimed at tissue regeneration. In addition, Muse cells were also determined to be able to be concentrated by stimulating mesenchymal cell fractions with various types of stress (WO2011/007900; Li, S., et al., Cancer Gene Therapy, Vol. 12, p. 600-607 (2005); Kuroda, Y., et al., Proc. Natl. Acad. Sci. USA, Vol. 107, p. 8639-8643 (2010); Wakao, S., et al., Proc. Natl. Acad. Sci. USA, Vol. 108, p. 9875-9880 (2011); Kuroda, Y., et al., Nat. Protoco., Vol. 8, p. 1391-1415 (2013)). However, there have yet to be any examples of the use of Muse cells for the prevention and/or treatment of kidney disease, and the obtaining of anticipated therapeutic effects has yet to be clearly determined.